Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Three experiments were conducted to study the effect of dietary L-tryptophan supplementation (250-1000 ppm) on lipid accumulation, an occurrence of hemorrhages and microsomal mixed function oxidase in the liver of laying hens. 2. Dietary L-tryptophan supplementation resulted in significant decreases in hepatic lipids, in particular triglyceride, and occurrence of hemorrhage in laying hens. 3. Hepatic lipid accumulation by estrogen injection in starved-refed growing chicks decreased as dietary tryptophan content increased. 4. Supplementation of L-tryptophan at 1000 mg/kg diet enhanced alanine aminotransferase activity in the hepatic tissue and at 500 mg/kg diet, increased cytochrome b5, a component of the mixed function oxidase, in the hepatic microsomes. 5. These results demonstrate that L-tryptophan alleviates fatty liver in laying hens and modifies microsomal mixed function oxidase in the liver.
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PMID:L-tryptophan alleviates fatty liver and modifies hepatic microsomal mixed function oxidase in laying hens. 135 43

Using data from 17 patients with liver cirrhosis and 3 patients with fatty liver, we have compared the utility of 3 hepatic imaging agents in the evaluation of hepatic functional reserve. Evaluated here were 99mTc-galactosyl human serum albumin (GSA) which is a new ligand for hepatic binding protein, 99mTc-N-pyridoxyl-5-methyl tryptophan (PMT) of a hepatobiliary agent, and 99mTc-Sn colloid. In each patient, we performed these 3 imaging studies within a week and also examined hepatic function tests (indocyanine green test, hepaplastin test, choline-esterase, etc). In each imaging study, serial images and dynamic data were obtained after the injection of 99mTc-GSA (185 MBq/3 mg), 99mTc-PMT (185 MBq), or 99mTc-Sn colloid (185 MBq). Using the obtained dynamic data, we analyzed the liver kinetics of the 3 agents based on 1 compartment model with 3 parameters (hepatic clearance, hepatic excretion rate, non-specific volume of distribution). From fitting the liver and heart data to this model, three unknown parameters were determined. Patlak plot was also applied in order to estimate liver uptake rate. Both curve fitting and Patlak plot could determine appropriate parameters in every study. In 99mTc-GSA, a nonlinear 3 compartment model was also applied in order to estimate hepatic blood flow, liver receptor density, and affinity of receptor-GSA binding separately. Using the obtained parameters, we analyzed the correlations between the parameters and the results of hepatic function tests. In all of the parameters, those obtained from 99mTc-GSA imaging showed the most significant statistical correlation with the results of hepatic function tests. From the present results, 99mTc-GSA imaging was concluded to be the best for evaluation of hepatic functional reserve.
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PMID:[The utility of quantitative 99mTc-GSA liver scintigraphy in the evaluation of hepatic functional reserve: comparison with 99mTc-PMT and 99mTc-Sn colloid]. 143 71

The amino acid composition of proteins from liver mitochondrial membranes has been studied in patients with normal liver, with biliary diseases and fatty liver, with obstructive jaundice or liver cirrhosis. A characteristic pattern of the amino acid composition in patients with normal liver has been found. In the mitochondrial membranes of patients with fatty liver tryptophan and lysine were decreased while [aspartic acid plus asparagine] and [glutamic acid plus glutamine] were increased compared to their counterpart in the normal liver. In patients with obstructive jaundice of short duration (less than two months) only a slight decrease in methionine content was found, while in the case of liver cirrhosis amino acid composition was markedly changed.
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PMID:Amino acid composition of human liver mitochondrial membranes in normal and pathological conditions. 186 76

Adult male Sprague-Dawley rats were treated with USP-grade L-tryptophan at a level of 250 mg/kg seven times over 14 d or three times over 3 d by gastric gavage. At autopsy liver specimens were prepared for histological study by stains specific for lipids, for glycoprotein and glycogen, and for fine structure by electron microscopy. Liver lipid did not accumulate as a result of tryptophan treatment. In a series of unfed animals, however, liver lipid had accumulated within 24 h of food withdrawal. Tryptophan has been implicated in fatty liver development by several reports that cite each other, but, in all cases but one, unfed animals were used, and the data show that liver lipid was already present in the unfed animals at the beginning of the experiment. Tryptophan has also been cited as causing abnormal liver morphology, but our evidence suggests that such observations are the result of artifact induced by frozen section preparation and not the result of tryptophan treatment. Our experiments indicate that tryptophan administered to rats at dosages in excess of those recommended for humans does not induce fatty liver or other morphological changes detectable by the methods described.
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PMID:Rat liver is not damaged by high dose tryptophan treatment. 848 97

The prevalence of a mutation of the codon for tryptophan 64 to arginine (Trp64Arg) in the beta3-adrenergic receptor gene was investigated by genotyping 261 Japanese subjects. The allelic frequency of this mutation was 0.18. Subjects with the homozygous W64R mutant alleles had a significantly higher prevalence of fatty liver, BMI, serum gamma-glutamyl transpeptidase, and serum leucine amino transpeptidase levels than those without the mutation. Individuals with this mutation also showed a higher fasting blood glucose level than those without this mutation. However, the prevalence of diabetes mellitus was no different between the three groups. These results suggest a potential association of the Trp64Arg mutation with higher morbidity of fatty liver and mild glucose intolerance.
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PMID:Association of the Trp64Arg mutation of the beta3-adrenergic receptor with fatty liver and mild glucose intolerance in Japanese subjects. 969 85

The effects of dietary orotic acid on the metabolism of tryptophan to niacin in weaning rats was investigated. The rats were fed with a niacin-free, 20% casein diet containing 0% (control diet) or 1% orotic acid diet (test diet) for 29 d. Retardation of growth, development of fatty liver, and enlargement of liver were observed in the test group in comparison with the control group. The concentrations of NAD and NADP in liver significantly decreased, while these in blood did not decrease compared to the control group. The formation of the upper metabolites of tryptophan to niacin such as anthranilic acid, kynurenic acid, and 3-hydroxyanthranilic acid were not affected, but the quinolinic acid and beyond, such as nicotinamide, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide, were significantly reduced by the administration of orotic acid. Therefore, the conversion ratio of tryptophan to niacin significantly decreased in the test group in comparison with the control group.
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PMID:Effects of fatty liver induced by niacin-free diet with orotic acid on the metabolism of tryptophan to niacin in rats. 1216 38

Liver fatty acid-binding protein (FABP) is able to bind to anionic phospholipid vesicles under conditions of low ionic strength. This binding results in the release of ligand, the fluorescent fatty acid analogue 11-dansylaminoundecanoic acid (DAUDA), with loss of fluorescence intensity (Davies, J. K., Thumser, A. E. A., and Wilton, D. C. (1999) Biochemistry 38, 16932-16940). Using a strategy of charge reversal mutagenesis, the potential role of specific cationic residues in promoting interfacial binding of FABP to anionic phospholipid vesicles has been investigated. Cationic residues chosen included those within the alpha-helical region (Lys-20, Lys-31, and Lys-33) and those that make a significant contribution to the positive surface potential of the protein (Lys-31, Lys-36, Lys-47, Lys-57, and Arg-126). Only three cationic residues make a significant contribution to interfacial binding, and these residues (Lys-31, Lys-36, and Lys-57) are all located within the ligand portal region, where the protein may be predicted to exhibit maximum disorder. The binding of tryptophan mutants, F3W, F18W, and C69W, to dioleoylphosphatidylglycerol vesicles, containing 5 mol% of the fluorescent phospholipid dansyldihexadecanoylphosphatidylethanolamine, was monitored by fluorescence resonance energy transfer (FRET). All three mutants showed enhanced dansyl fluorescence due to FRET on addition of phospholipid to protein; however, this fluorescence was considerably greater with the F3W mutant, consistent with the N-terminal region of the protein coming in close proximity to the phospholipid interface. These results were confirmed by succinimide quenching studies. Overall, the results indicate that the portal region of liver FABP and specifically Lys-31, Lys-36, and Lys-57 are involved in the interaction with the interface of anionic vesicles and that the N-terminal region of the protein undergoes a conformational change, resulting in DAUDA release.
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PMID:Effect of charge reversal mutations on the ligand- and membrane-binding properties of liver fatty acid-binding protein. 1237 51

Liver fatty acid-binding protein (FABP) binds a variety of non-polar anionic ligands including fatty acids, fatty acyl CoAs, and bile acids. Previously we prepared charge reversal mutants and demonstrated the importance of lysine residues within the portal region in ligand and membrane binding. We have now prepared several tryptophan-containing mutants within the portal region, and one tryptophan at position 28 (L28W) has proved remarkably effective as an intrinsic probe to further study ligand binding. The fluorescence of the L28W mutant was very sensitive to fatty acid and bile acid binding where a large (up to 4-fold) fluorescence enhancement was obtained. In contrast, the binding of oleoyl CoA reduced tryptophan fluorescence. Positive cooperativity for fatty acid binding was observed while detailed information on the orientation of binding of bile acid derivatives was obtained. The ability of bound oleoyl CoA to reduce the fluorescence of L28W provided an opportunity to demonstrate that fatty acyl CoAs can compete with fatty acids for binding to liver FABP under physiological conditions, further highlighting the role of fatty acyl CoAs in modulating FABP function in the cell.
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PMID:Tryptophan insertion mutagenesis of liver fatty acid-binding protein: L28W mutant provides important insights into ligand binding and physiological function. 1554 5

Nonalcoholic fatty liver disease is one of the most common liver diseases. L-tryptophan and its metabolite serotonin are involved in hepatic lipid metabolism and inflammation. However, it is unclear whether L-tryptophan promotes hepatic steatosis. To explore this issue, we examined the role of L-tryptophan in mouse hepatic steatosis by using a high fat and high fructose diet (HFHFD) model. L-tryptophan treatment in combination with an HFHFD exacerbated hepatic steatosis, expression of HNE-modified proteins, hydroxyproline content, and serum alanine aminotransaminase levels, whereas L-tryptophan alone did not result in these effects. We also found that L-tryptophan treatment increases serum serotonin levels. The introduction of adenoviral aromatic amino acid decarboxylase, which stimulates the serotonin synthesis from L-tryptophan, aggravated hepatic steatosis induced by the HFHFD. The fatty acid-induced accumulation of lipid was further increased by serotonin treatment in cultured hepatocytes. These results suggest that L-tryptophan increases the sensitivity to hepatic steatosis through serotonin production. Furthermore, L-tryptophan treatment, adenoviral AADC introduction, and serotonin treatment induced phosphorylation of the mammalian target of rapamycin (mTOR), and a potent mTOR inhibitor rapamycin attenuated hepatocyte lipid accumulation induced by fatty acid with serotonin. These results suggest the importance of mTOR activation for the exacerbation of hepatic steatosis. In conclusion, L-tryptophan exacerbates hepatic steatosis induced by HFHFD through serotonin-mediated activation of mTOR.
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PMID:L-tryptophan-mediated enhancement of susceptibility to nonalcoholic fatty liver disease is dependent on the mammalian target of rapamycin. 2184 Oct

Although new research technologies are constantly used to look either for genes or biomarkers in the prediction of metabolic syndrome (MS), the pathogenesis and pathophysiology of this complex disease remains a major challenge. Interestingly, Cheng et al recently investigated possible pathways underlying MS by high-throughput metabolite profiling in two large and well characterized community-based cohorts. The authors explored by liquid chromatography and mass spectrometry the plasma concentrations of 45 distinct metabolites and examined their relation to cardiometabolic risk, and observed that metabolic risk factors such as obesity, insulin resistance (IR), high blood pressure, and dyslipidemia were associated with several metabolites, including branched-chain amino acids, other hydrophobic amino acids, tryptophan breakdown products, and nucleotide metabolites. In addition, the authors found a significant association of IR traits with glutamine, glutamate and the glutamine-to-glutamate ratio. These data provide new insight into the pathogenesis of MS-associated phenotypes and introduce a crucial role of glutamine-cycling pathway as prominently involved in the development of metabolic risk. We consider that the hypothesis about the role of abnormal glutamate metabolism in the pathogenesis of the MS is certainly challenging and suggests the critical role of the liver in the global metabolic modulation as glutamate metabolism is linked with aminotransferase reactions. We discuss here the critical role of the "liver metabolism" in the pathogenesis of the MS and IR, and postulate that before fatty liver develops, abnormal levels of liver enzymes, such as alanine and aspartate aminotransferases might reflect high levels of hepatic transamination of amino acids in the liver.
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PMID:Alanine and aspartate aminotransferase and glutamine-cycling pathway: their roles in pathogenesis of metabolic syndrome. 2287 26


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